5WIT

Crystal structure of the Thermus thermophilus 70S ribosome in complex with pikromycin and bound to mRNA and A-, P- and E-site tRNAs at 2.6A resolution

これはPDB形式変換不可エントリーです。

5WIT の概要

• エントリーDOI: 10.2210/pdb5wit/pdb
• 分子名称: 23S Ribosomal RNA, 50S ribosomal protein L14, 50S ribosomal protein L15, ... (62 entities in total)
• 機能のキーワード: macrolide, antibiotic, inhibitor, inhibition of translation, peptidyl transferase center, ribosome
• 由来する生物種: Escherichia coli; 詳細
• タンパク質・核酸の鎖数: 112
• 化学式量合計: 4561947.66

構造登録者

Almutairi, M.M.,Svetlov, M.S.,Hansen, D.A.,Khabibullina, N.F.,Klepacki, D.,Kang, H.Y.,Sherman, D.H.,Vazquez-Laslop, N.,Polikanov, Y.S.,Mankin, A.S. (登録日: 2017-07-20, 公開日: 2018-02-14, 最終更新日: 2025-03-19)

主引用文献

Almutairi, M.M.,Svetlov, M.S.,Hansen, D.A.,Khabibullina, N.F.,Klepacki, D.,Kang, H.Y.,Sherman, D.H.,Vazquez-Laslop, N.,Polikanov, Y.S.,Mankin, A.S.
Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins.
Nucleic Acids Res., 45:9573-9582, 2017

PubMed Abstract: Antibiotics methymycin (MTM) and pikromycin (PKM), co-produced by Streptomyces venezuelae, represent minimalist macrolide protein synthesis inhibitors. Unlike other macrolides, which carry several side chains, a single desosamine sugar is attached to the macrolactone ring of MTM and PKM. In addition, the macrolactone scaffold of MTM is smaller than in other macrolides. The unusual structure of MTM and PKM and their simultaneous secretion by S. venezuelae bring about the possibility that two compounds would bind to distinct ribosomal sites. However, by combining genetic, biochemical and crystallographic studies, we demonstrate that MTM and PKM inhibit translation by binding to overlapping sites in the ribosomal exit tunnel. Strikingly, while MTM and PKM readily arrest the growth of bacteria, ∼40% of cellular proteins continue to be synthesized even at saturating concentrations of the drugs. Gel electrophoretic analysis shows that compared to other ribosomal antibiotics, MTM and PKM prevent synthesis of a smaller number of cellular polypeptides illustrating a unique mode of action of these antibiotics.

PubMed: 28934499
DOI: 10.1093/nar/gkx673

実験手法

X-RAY DIFFRACTION (2.6 Å)